The PPARγ K422Q mutation does not contribute to troglitazone inefficiency in colon cancer treatment

被引:7
作者
Bouancheau, D
Buecher, B
Jarry, A
Simon, B
Masson, D
Cassagnau, E
Hamelin, R
Laboisse, CL
Bézieau, S
Denis, MG
机构
[1] Fac Med, INSERM, U539, UFR Med, F-44035 Nantes, France
[2] CHU Nantes, Hotel Dieu, Gastroenterol Serv, F-44035 Nantes, France
[3] Fac Med, ADN, Lab Etud Polymorphisme, F-44035 Nantes, France
[4] CEPH, INSERM, U434, Paris, France
关键词
PPAR gamma; mutation; colon cancer; allele-specific PCR;
D O I
10.1016/j.canlet.2004.10.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Peroxisome proliferator-activated receptor gamma (PPAR gamma) ligands inhibit cell growth of colorectal cancer cells in most experimental models, but no significant effect could be observed in patients with colorectal cancer. We therefore, screened human colorectal tumors to determine the prevalence of the PPAR gamma K422Q loss-of-function mutation, recently identified in 50% of colonic cancer cell lines. A sensitive allele-specific real-time amplification assay was developed and 170 colorectal primary tumors and 12 liver metastasis were analyzed. We did not find the K422Q mutation in any of these samples. We can therefore exclude this alteration as a mechanism of resistance to PPAR gamma ligands in patients with colon cancer. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:111 / 116
页数:6
相关论文
共 14 条
[1]   Cyclo-oxygenase-2 over-expression in sporadic colorectal carcinoma without lymph node involvement [J].
Buecher, B ;
Heymann, MF ;
Lièvre, A ;
Nguyen, JM ;
Wilson, K ;
Bézieau, S ;
Mosnier, JF ;
Galmiche, JP ;
Blottière, HM .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2003, 18 (07) :731-740
[2]   Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-γ ligand troglitazone in patients with liposarcoma [J].
Demetri, GD ;
Fletcher, CDM ;
Mueller, E ;
Sarraf, P ;
Naujoks, R ;
Campbell, N ;
Spiegelman, BM ;
Singer, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3951-3956
[3]   APIC-dependent suppression of colon carcinogenesis by PPARγ [J].
Girnun, GD ;
Smith, WM ;
Drori, S ;
Sarraf, P ;
Mueller, E ;
Eng, C ;
Nambiar, P ;
Rosenberg, DW ;
Bronson, RT ;
Edelmann, W ;
Kucherlapati, R ;
Gonzalez, FJ ;
Spiegelman, BM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (21) :13771-13776
[4]   Peroxisome proliferator-activated receptor γ-mediated differentiation -: A mutation in colon cancer cells reveals divergent and cell type-specific mechanisms [J].
Gupta, RA ;
Sarraf, P ;
Mueller, E ;
Brockman, JA ;
Prusakiewicz, JJ ;
Eng, C ;
Willson, TM ;
DuBois, RN .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (25) :22669-22677
[5]  
Ikezoe T, 2001, CANCER RES, V61, P5307
[6]  
Koeffler HP, 2003, CLIN CANCER RES, V9, P1
[7]   A phase II study of troglitazone, an activator of the PPARγ receptor, in patients with chemotherapy-resistant metastatic colorectal cancer [J].
Kulke, MH ;
Demetri, GD ;
Sharpless, NE ;
Ryan, DP ;
Shivdasani, R ;
Clark, JS ;
Speigelman, BM ;
Kim, H ;
Mayer, RJ ;
Fuchs, CS .
CANCER JOURNAL, 2002, 8 (05) :395-399
[8]   Peroxisome-proliferator-activated receptors and cancers: Complex stories [J].
Michalik, L ;
Desvergne, B ;
Wahli, W .
NATURE REVIEWS CANCER, 2004, 4 (01) :61-70
[9]   Effects of ligand activation of peroxisome proliferator-activated receptor γ in human prostate cancer [J].
Mueller, E ;
Smith, M ;
Sarraf, P ;
Kroll, T ;
Aiyer, A ;
Kaufman, DS ;
Oh, W ;
Demetri, G ;
Figg, WD ;
Zhou, XP ;
Eng, C ;
Spiegelman, BM ;
Kantoff, PW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (20) :10990-10995
[10]   Chromosomal changes and progressive tumorigenesis of human bronchial epithelial cell lines [J].
Ohnuki, Y ;
Reddel, RR ;
Bates, SE ;
Lehman, TA ;
Lechner, JF ;
Harris, CC .
CANCER GENETICS AND CYTOGENETICS, 1996, 92 (02) :99-110